The Best Pain Killers

Last updated by Dr Sarah Brewer on October 24th, 2018

Pain is an important symptom that lets you know when something is wrong. But once pain has alerted you to an injury, inflammation, infection or other disease, and the underlying cause is addressed, pain has done its job. The priority is then to control the pain with the best pain killers to prevent persistent suffering. Yet between one-third and one-half of the population experience long-term (chronic) pain, which is an astonishing number. In some cases, this is because the pain-killer you are using is ineffective and switching to another would work better.

Best pain killers over the counter

Different painkillers work in different ways and the genes you have inherited will affect how well you respond. Some people quickly metabolise a particular drug so it rapidly falls to ineffective levels. Others inherit receptors that don’t interact or respond to some types of analgesic.

On average, each painkiller is only effective in two out of three people – this is true of both over-the-counter pain killers you buy yourself, and some prescribed analgesics such as the non-steroidal anti-inflammatory drugs (NSAIDs).

If you don’t respond to one painkiller, you may respond to another. An exhaustive review of all the evidence from clinical trials that the most effective analgesic is a combination of ibuprofen plus paracetamol which has a success rate of up to 70%, where success was defined as cutting pain by at least half over four to six hours, compared with an inactive placebo. This level of pain relief is considered effective treatment for improving quality of life.

The best pain killer is ibuprofen and paracetamol combined

According to a gold-standard, Cochrane systematic review, the effectiveness of different non-prescription (over the counter) oral pain killers in thousands of people, is as follows:

The combination of ibuprofen plus paracetamol (acetaminophen) was significantly more effective at relieving pain than any other oral, over-the-counter pain killer, with a success rate of up to 70%. That means seven out of ten people taking a product that contains ibuprofen plus paracetamol (acetaminophen) will experience effective pain relief (symptoms reduced by at least half).

Fast-acting formulations of ibuprofen, and those combining ibuprofen plus caffeine were the next most effective, with success rates of between 50% and 60%.

Paracetamol alone had a success rate of 43% at doses of 500mg but larger doses were less effective. Aspirin was the least effective pain killer overall, with a success rate of only 11%.

There were no clinical trials to show how well codeine or dihydrocodeine worked in this particular analysis.

Only a few products include the combination of ibuprofen and paracetamol (acetaminophen), however, such as Nuramol which is available from pharmacies in the UK.

You can take paracetamol and ibuprofen together as separate products, however. This is safe for anyone aged 16 or over, as there is no known harmful interaction between paracetamol (acetaminophen) and ibuprofen.

Another way to obtain the synergistic benefit is to alternative doses of ibuprofen and paracetamol, so you take one or the other, every 4 to 6 hours, ensuring that you don’t take more than the recommended doses of either in any 24 hour period.

If in doubt, check with a pharmacist or doctor.

You should also seek advice if you need to take pain killers for more than three days, to find out the underlying cause, and to see if another treatment might suit you better.

Which painkiller works best for you?

While the combination of ibuprofen plus paracetamol (acetaminophen) worked best for the thousands of people assessed, everyone is different and you may respond better to aspirin, or less well to ibuprofen than average.

You may already know which pain killers work best for you as an individual, and intuitively select aspirin, paracetamol, ibuprofen or codeine based on your past experience of their effectiveness for you.

If you are unhappy with your current non-prescription painkiller, however, and haven’t already tried a combination of ibuprofen plus paracetamol, this appears to be the most effective non-prescription analgesic for most people.

Below is a full overview that explains how aspirin, paracetamol, ibuprofen, codeine and dihydrocodeine work, how effective they are, and their possible side effects. I have also provided links to the relevant patient information leaflets in case you need them.

Over-the-counter painkillers

Many people rely on over the counter pain killers to treat mild to moderate aches and pains. In general, take the lowest effective dose to reduce the risk of side effects.

For self-limiting types of pain, such as a tension headache, you may only need one or two doses of a painkiller. For treating persistent types of pain, such as joint pain due to osteoarthritis, your doctor may suggest taking a painkiller regularly, as regular doses of an analgesic can be more effective for keeping pain at bay than waiting until pain breaks through to treat it. But regular daily use can increase the risk of side effects, including rebound headaches, as described below.

Unfortunately, there is a growing recognition that the long-term use of painkillers – even paracetamol – is not as safe as once believed, and may increase the long-term risk of heart, liver or kidney problems.

Pain-relieving topical creams and gels are therefore growing in popularity and are recommended by most doctors as a first-line treatment for muscle and joint aches and pains.

Medication overuse headache

Regular use of over-the-counter pain killers can cause the very symptoms you are trying to avoid, if not used correctly. Known as rebound headache, or medication overuse headache, the frequent or prolong use of painkillers can result in a rebound or worsening headache. This is especially common in people who are taking pain killers to treat migraine.

When the effects of a pain killer wears off, you may experience a withdrawal reaction which prompts you take more medication. This leads to another headache, and the need to take yet more medication resulting in a vicious cycle of more frequent, worsening, daily headaches.

Aspirin, sinus-relief medications, paracetamol (acetaminophen), non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, and opiates such as codeine have all been found to cause rebound headaches when used regularly. Medication overuse headache is especially likely if you consume high amounts of caffeine.

To avoid rebound headaches, take the lowest possible dose of painkiller, and do not use analgesics for more than a day or two per week. Don’t take more than the recommended dose and, if you have daily pain, seek medical advice.

Which pain killer formulation is best?

Soluble painkillers, and those that dissolve in the mouth, work more quickly than tablets swallowed whole, as the active ingredients are more readily absorbed into the bloodstream and get to work more quickly.

However, dispersible tablets use sodium bicarbonate to make them fizz, and can contain as much sodium as two-and-a-half packets of ready-salted crisps. Because of this, soluble medicines are no longer routinely recommended, especially if you have high blood pressure.

Controlled (sustained) release preparations can be taken less often and help to maintain a constant blood level of the pain killing drug. They may be more effective for constant, nagging sorts of pain.

For sports injuries, a rub-on gel or cream may work as well – or better – than a drug taken by mouth.

Painkiller additives and what they do

Many analgesic products combine a painkiller with caffeine, vitamin C, antihistamines or other additives to boost their effectiveness.

Caffeine is designed to speed up the reaction of other ingredients. It also helps perk you up and feel more energised. Caffeine may, however, aggravate stomach irritation when used with aspirin, and may increase the chance of withdrawal or rebound headaches – especially if you also have a high caffeine intake from caffeinated drinks.

A tablet containing 50mg caffeine provides the same amount of caffeine as an average cup of coffee. Research shows that caffeine withdrawal headaches can occur when regular use of an over-the-counter analgesic containing caffeine is stopped. This can occur if you consume the equivalent of two and a half cups of coffee a day (150mg caffeine).

Sodium bicarbonate helps to settle an upset stomach when combined with paracetamol and may be used in products designed to relieve headache plus indigestion or hangover. However, sodium can increase blood pressure in some people.

Vitamin C helps to mop up some of the damaging chemicals (free radicals) released during inflammation, and can improve symptoms associated with colds, for example.

Hyoscine may be added to pain relief products designed to reduce cramping of the intestines and to treat period cramps. Hyoscine should not be used by anyone with glaucoma or urinary difficulties. Hyoscine can cause dry mouth, drowsiness or blurred vision.

Antihistamines (eg diphenhydramine, doxylamine, promethazine, buclizine, cyclizine) are used to reduce blocked nose and to relieve allergic symptoms eg hayfever. Some suppress cough. Buclizine and cyclizine help to reduce nausea and vomiting and are included in some anti-migraine preparations. Antihistamines may cause drowsiness, dry mouth or blurred vision.

Decongestants (eg pseudoephedrine, triprolidine, phenylephrine, phenylpropanolamine) are added to some cold, influenza and sinusitis remedies to help clear a blocked nose

Coping with pain

If you experience mild to moderate pain, try to rest and take things easy while your chosen pain killer gets to work. Take your mind off things by reading, watching television, listening to music.

Write down how you feel – researchers have found that writing about negative experiences seems to reduce pain perception.

Rubbing the area or applying hot or cold packs can reduce pain by stimulating other nerve endings that block transmission of pain messages.

When to seek medical help

Like all drugs, painkillers can have side effects. If you are not sure which analgesic is most likely to suit you, always seek advice from a pharmacist or doctor. Always read the information provided with your painkillers and never exceed the stated dose.

If pain persists, or becomes worse, always seek medical advice – both to find out the cause, and to see if you need a stronger prescription-only treatment.

Always seek medical advice if you develop:

Severe or worsening pain.

A recurrent pain that keeps coming back such as a headache, indigestion, abdominal pain or chest ache – this is especially important if you notice other related symptoms such as weight loss, tiredness all the time, lethargy, stiffness, swelling, high fever or change in bowel habit.

Sudden chest pain, especially if it is tight or crushing, it is worse on breathing in or accompanied by breathlessness, cough, or phlegm stained with pus or blood.

Abdominal pain during pregnancy.

Side effects related to pain medication.

Any pain that concerns you.

Aspirin pain killers

Aspirin is used to treat mild to moderate pain, and to reduce inflammation and fever. Low doses (eg 75mg, known as mini-aspirin), are used to thin the blood and reduce the risk of unwanted blood clots.

How aspirin reduces pain

Aspirin works by inhibiting two enzymes (COX-1 and COX-2) that generate substances (prostaglandins, thromboxanes) which stimulate pain receptors to trigger sensations of pain.

COX-1 is mainly active in the gastrointestinal tract and is needed to maintain the protective mucus coating of the stomach. COX-2 on the other hand is active at sites of inflammation.

Dose: A typical dose is 300mg – 600mg aspirin after meals, at intervals of at least four hours. Always follow instructions on the label as different products vary.

How effective is aspirin for pain relief?

Aspirin is the least effective of all over-the-counter painkillers. At a dose of 500mg it has a success rate of just 11%, meaning that it only really helps one out of 10 people. This is no better than inactive placebo.

At higher doses of 600mg to 1g, aspirin has a success rate of around 30% (and helps four out of ten people) but higher doses increase the risk of side effects.

Possible side effects of aspirin

Aspirin irreversibly blocks the enzyme, COX-1, which as well as reducing pain, is also needed to maintain the protective mucus lining of the stomach.

By inhibiting COX-1, aspirin can increase exposure of the stomach wall to stomach acid attack – especially if a swallowed tablet sits up against the stomach wall when it can literally burn a whole into the stomach wall. Aspirin can lead to stomach inflammation (gastritis) and bleeding due to peptic ulceration. Bleeding can be profuse because of the blood-thinning effects of aspirin – even low doses reduce the stickiness of platelets and prolong bleeding time.

In order to minimise stomach irritation, select aspirin with a gastro-resistant coating. Soluble or effervescent forms can also minimise stomach irritation, but these formulations contain sodium and are best avoided if you have high blood pressure.

Paracetamol (acetaminophen) pain killers

Paracetamol – also known as acetaminophen – is used to treat mild to moderate pain and fever. It does not reduce inflammation.

How paracetamol reduces pain

The exact way in which paracetamol suppresses pain is uncertain. It may have a direct action on the brain to reduce both pain and fever, or it may have a weak, aspirin-like action to inhibit enzymes (COX-1 and COX-2) involved in generating painful stimuli.

Unlike aspirin, paracetamol does not reduce swelling or stiffness and does not irritate the stomach lining.

Paracetamol (acetaminophen) is used to treat headache, colds and influenza, plus minor aches without inflammation such as period pains, neuralgia and dental pain.

Dose: A typical adult dose is 500mg – 1g at intervals of four to six hours, up to a maximum dose of 4g daily. Do not take more than 8 x 500mg tablets in 24 hours. If you drink more than three alcoholic drinks per day, talk to your doctor before taking paracetamol and don’t use more than 2 grams (4 x 500mg tablets) per day. Children: as on instruction leaflet, according to age.

Before taking paracetamol, it is best to consult a pharmacist to check whether or not paracetamol will suit you. This is especially important if you are taking any prescribed medicines.

How effective is paracetamol for pain relief?

On its own, 500mg paracetamol has a success rate of around 43% meaning it only helps around 4 out of 10 people. In fact, researchers have found that, for every 3.5 people taking it, only one would experience good pain relief. Oddly, there is no evidence that higher doses (600mg to 1g) are more effective – in fact, they appear to be less effective than the 500mg dose!

A study published in the British Medical Journal, which looked at the results from 13 clinical trials, concluded that paracetamol is not effective for reducing back pain, and that it provides only minimal, short-term benefit for people with osteoarthritis of the hip or knee. The most likely explanation is that these conditions are associated with low-grade inflammation, and paracetamol lacks any anti-inflammatory action.

If paracetamol works for you, however, there is no reason to stop taking it – everyone responds to medicines in different ways.

Possible side effects of paracetamol (acetaminophen)

Paracetamol can damage the liver and kidneys if the recommended dose is exceeded. Always check labels and do not take more than one product containing paracetamol at a time.

There is a growing understanding that paracetamol is not as safe as once believed. The long-term use of paracetamol is now discouraged due to concerns that may increase the risk of heart attack or stroke. The results from four studies suggest that long-term use of paracetamol is associated with a 19% to 68% higher risk of developing cardiovascular problems. Another study found that long-term use of paracetamol was associated with an 11% to 49% increased the risk of intestinal bleeding.

Researchers have also found that long-term use of acetaminophen (paracetamol) is associated with a 21% increase in self-reported hearing loss. Whether these findings relate to the use of the painkiller, or to the underlying conditions for which it is used, remains uncertain.

Rare side effects of paracetamol include skin rash and blood disorders.

Do not take paracetamol (except under medical supervision) if you have:

A high alcohol intake (increased risk of liver damage)

Kidney or liver problems

If in doubt, or if you are taking any other prescribed medicines, consult a pharmacist to check whether or not paracetamol will suit you.

Ibuprofen pain killers

Ibuprofen is related to aspirin and is classed as a non-steroidal anti-inflammatory drug (NSAID). Ibuprofen is used to relieve the pain of sports injuries (eg sprained ligaments, strained muscles), stiff or painful joints, heavy or painful periods, dental pain and headaches.

How ibuprofen reduces pain

Like aspirin, ibuprofen works by inhibiting cyclo-oxygenase enzymes (COX-1 and COX-2) which are involved in the generation of pain.

In single doses, ibuprofen reduces fever and has a pain-killing action comparable to that of paracetamol. When used in regular full dosage, ibuprofen has an additional anti-inflammatory action to reduce redness, stiffness and swelling (but beware of rebound headache).

Dose: A typical adult dose is 200mg – 400mg ibuprofen, after food, at intervals of at least four hours. Do not take more than 6 x 200mg tablets in 24 hours unless otherwise instructed by a doctor. Always follow the on-pack instructions. Higher doses are available on prescription for use under medical supervision.

How effective is ibuprofen for pain relief?

Fast-acting formulations of ibuprofen at doses of 200 mg and 400 mg, and ibuprofen 200 mg plus caffeine 100 mg, have a success rate of over 50%, meaning they provide effective pain relief in at least 5 out of 10 people.

As mentioned above, the combination of ibuprofen 400mg plus paracetamol 1g is the most effective over-the-counter, non-prescription pain killer, with a success rate of 70%.

Possible side effects of ibuprofen

The side effects of ibuprofen can include heartburn, indigestion, feeling sick, diarrhoea.

The long-term use of NSAIDs such as ibuprofen is limited by their intestinal side effects as they can irritate the stomach and can cause gastroduodenal ulcers/perforation and bleeding.

A review of gastro-intestinal risks found that people who take daily doses of ibuprofen are 84% more likely to experience upper gastro-intestinal complications (bleeding, perforation or obstruction) than non-users.

The long-term use of NSAIDs also increases the risk of heart attack, heart failure, kidney problems and stroke.

Research suggests that taking long-term ibuprofen at high doses (prescription-only doses of more than 1,200mg per day) can increase the relative risk of experiencing a heart attack or stroke by 78%. Low doses do not appear to significantly increase the risk, however.

Rarer side effects include skin rashes and breathing problems in people with aspirin-sensitive asthma.

A review of 23 studies, involving over 92,500 people found that taking non-steroidal anti-inflammatory drugs such as ibuprofen as associated with a 21% increase in self-reported hearing loss. These finding have not been confirmed by audiometry testing and could be due to the underlying painful or inflammatory condition present rather than to the pain killers themselves.

Ibuprofen should not be used (except under medical supervision) by:

children under 12 (unless prescribed by a doctor for reducing fever)

those with a history of peptic ulcers, asthma, kidney, heart or liver problems or a blood clotting disorders

women who are pregnant or breastfeeding

NB Ibuprofen can interact with other medicines, including anticoagulants and drugs used to treat high blood pressure. Always seek advice form a pharmacist before taking ibuprofen with other medicines.

Codeine pain killers

Codeine is a naturally occurring constituent of opium and is classed as an opiate pain-killer. It is closely related to morphine, but is much less potent. Codeine is used to relieve mild to moderate pain, to suppress cough, and to treat diarrhoea. These effects make it particularly useful for treating pain associated with coughing, and pain associated with diarrhoea (eg gastroenteritis, and some forms of irritable bowel syndrome).

Codeine is too constipating for long-term use on its own, and is usually combined with other analgesics. It helps to boost the effects of other analgesics such as aspirin, paracetamol or ibuprofen. The combination of codeine plus aspirin is particularly effective, and gives a better result than expected when used together.

How codeine relieves pain

Codeine works directly on the brain, spinal cord and peripheral nerves to reduce the transmission of pain signals, and the way pain is perceived in the brain. It changes the way you feel pain so that, although it may still be there, it no longer seems to matter.

Dose: Depends on the formulation and how much paracetamol or aspirin is also present. See instructions provided with each product.

How effective is codeine for pain relief?

When used alone, only one in 16 people taking codeine phosphate at a dose of 60mg will receive effective pain relief. When combined with paracetamol (acetaminophen) however, one in two people obtain effective pain relief.

There is a dose-response effect, so that the combination of codeine phosphate 60mg plus paracetamol (acetaminophen) 600mg is twice as effective as codeine phosphate 30mg plus paracetamol (acetaminophen) 300mg when used for post-operative pain relief. However, higher doses of codeine increase the chance of side effects.

Codeine-based medicines have been found to reduce cough severity, but not cough frequency.

Possible side effects of codeine

The common side effects of codeine phosphate include drowsiness, dizziness, headache, nausea and vomiting.

Those with a history of asthma, seizures, kidney, liver, thyroid or prostate problems.

Anyone with previous addiction problems.

Young children except under advice from a doctor or pharmacist – products vary depending on formulation.

Dihydrocodeine for pain

Dihydrocodeine is an opiate pain killer, similar to codeine, but more powerful. Dihydrocodeine is usually reserved to treat acute moderate pain which has not responded to paracetamol, ibuprofen or aspirin alone. It can be used to treat acute, moderate headache, migraine, period pains, dental pain, pain associated with cough, muscle pain and back ache.

Dose: Depends on the formulation and how much paracetamol is also present. See instructions provided with each product.

About Dr Sarah Brewer

QUORA EXPERT - TOP WRITER 2018
Dr Sarah Brewer MSc (Nutr Med), MA (Cantab), MB, BChir, RNutr, MBANT, CNHC qualified from Cambridge University with degrees in Natural Sciences, Medicine and Surgery. After working in general practice, she gained a master's degree in nutritional medicine from the University of Surrey. Sarah is a registered Medical Doctor, a registered Nutritionist and a registered Nutritional Therapist. She is an award winning author of over 60 popular self-help books and a columnist for Prima magazine.

2 thoughts on “The Best Pain Killers”

I have a knee injury. My doc had stopped serving me enough painkillers and I am afraid of doing online purchase of my stuff without prescription so do you guys have any treatment or suggestion for me so I can still survive to my pain.

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